ABSTRACT
The development of robust and reliable methods for the construction of C(sp2)-C(sp3) bonds is vital for accessing an increased array of structurally diverse scaffolds in drug discovery and development campaigns. While significant advances towards this goal have been achieved using metallaphotoredox chemistry, many of these methods utilise photocatalysts based on precious-metals due to their efficient redox processes and tuneable properties. However, due to the cost, scarcity, and toxicity of these metals, the search for suitable replacements should be a priority. Here, we show the use of commercially available heterogeneous semiconductor graphitic carbon nitride (gCN) as a photocatalyst, combined with nickel catalysis, for the cross-coupling between aryl halide and carboxylic acid coupling partners. gCN has been shown to engage in single-electron-transfer (SET) and energy-transfer (EnT) processes for the formation of C-X bonds, and in this manuscript we overcome previous limitations to furnish C-C over C-O bonds using carboxylic acids. A broad scope of both aryl halides and carboxylic acids is presented, and recycling of the photocatalyst demonstrated. The mechanism of the reaction is also investigated.
ABSTRACT
A general protocol for the europium-catalyzed rearrangement of aryl-pentadienyl-ethers is described. The mode of rearrangement and product formation in this reaction was solely determined by the aryl substituent para to the phenol. If the para-position is occupied by a substituent, the substrate undergoes a [3,3] rearrangement to the ortho-position to form a prochiral branched diene. In turn, a free para-position in the starting material allows the reaction to proceed via a [5,5] rearrangement and leads to a linear conjugated diene product. The severely underdeveloped and synthetically valuable [5,5] rearrangement was investigated in terms of scope and mechanism.
ABSTRACT
The ability to construct C(sp3 )-C(sp3 ) bonds from easily accessible reagents is a crucial, yet challenging endeavor for synthetic organic chemists. Herein, we report the realization of such a cross-coupling reaction, which combines N-sulfonyl hydrazones and C(sp3 )-H donors through a diarylketone-enabled photocatalytic hydrogen atom transfer and a subsequent fragmentation of the obtained alkylated hydrazide. This mild and metal-free protocol was employed to prepare a wide array of alkyl-alkyl cross-coupled products and is tolerant of a variety of functional groups. The application of this chemistry further provides a preparatively useful route to various medicinally-relevant compounds, such as homobenzylic ethers, aryl ethyl amines, ß-amino acids and other moieties which are commonly encountered in approved pharmaceuticals, agrochemicals and natural products.
